Crystallization crystalline salt formation

The formation of acyl halide-Lewis acid complexes have been observed by several methods. For example, both 1 1 and 1 2 complexes of acetyl chloride, with AICI3 can be observed by NMR spectroscopy. The existence of acylium ions has been demonstrated by X-ray diffraction studies on crystalline salts. For example, crystal structure determinations have been reported for /i-methylphenylacylium and acetylium ions as SbFg salts. There is also a good deal of evidence from NMR measurements which demonstrates that acylium ions can exist in nonnucleophilic solvents. " The positive charge on acylium ions is delocalized onto the oxygen atom. This delocalization is demonstrated in particular by the short O—C bond lengths in acylium ions, which imply a major contribution from the structure having a triple bond ... 

The mild detonations reported when the crystalline salt was disturbed [1] were thought to have been caused by presence of solvent ether in the crystals (6 mols of water may be replaced by 2 of ether) [2], This was later confirmed [3], and the formation of ethyl nitrate or diethyloxonium nitrate may have been involved, as the anhydrous salt functions as a powerful nitrator. Solutions of the nitrate in ether should not be exposed to sunlight to avoid the possibility of explosions. 

The physical form of the salt must be taken into account and several issues must be considered (Serajuddin and Pudipeddi, 2002). Forexample, amorphous material might result. Even if crystalline, the salt form might prove to be polymorphic. On crystallization or recrystallization, formation of a hydrate or a solvate might occur, and the effect of temperature and humidity on this form should be investigated. Both the physical and chemical stability of the different candidate salt forms in the solid state will ultimately deLne the optimal form of the drug. 

In principle, any of the photoproducts shown in Table 4 could have been prepared in enantiomerically pure form by irradiating their achiral precursors in solution to form a racemate and then separating the enantiomers by means of the classical Pasteur resolution procedure [36]. This sequence is shown in the lower half of Fig. 3. The top half of Fig. 3 depicts the steps involved in the solid-state ionic chiral auxiliary method of asymmetric synthesis. The difference between this approach and the Pasteur method is one of timing. In the ionic chiral auxiliary method, salt formation between the achiral reactant and an optically pure amine precedes the photochemical step, whereas in the Pasteur procedure, the photochemical step comes first and is followed by treatment of the racemate with an optically pure amine to form a pair of diastereomeric salts. The two methods are similar in that the crystalline state is crucial to their success. The Pasteur resolution procedure relies on fractional crystallization for the separation of the diastereomeric salts, and the ionic chiral auxiliary approach only gives good ees when the photochemistry is carried out in the crystalline state. 

There is much experimental evidence for the formation of complex oxy-ions in solutions of vanadates, niobates, and tantalates. We describe in Chapters 12 and 13 the structures of some crystalline vanadates here we note only certain finite complex ions which exist both in solution and in crystalline salts. The ion of Fig. 11.3(a) has been shown to exist in the salts Na7H(Nb60i9). 15 H20. Light scattering from an aqueous solution of Kg(Ta60i9). I6H2O indicates that the anion species contains 6 Ta atoms and is presumably similar to the ion in the crystal. ... 

Examining the inclusion of crystalline compounds Uke salts or metal oxides, it is a frequent observation that the two-dimensional confinement of the space of crystallization causes the formation of structures that differ sometimes completely from those found in the bulk phase. Antimony(III) oxide and potassium iodide may serve as examples here. For the Sb203-filaments inside nanotubes a valentinite structure with a lattice distortion inflicted by the outer restriction is observed (Figure 3.79d). NormaUy, this phase is found at high pressures. At standard conditions, the Sb203 adopts as cubic senarmonite structure with discrete Sb40,5-units. 

Early lots of varenicline were routinely generated through reduction of 8 to the corresponding diaminobenzazepine 9 and condensation of 9 with glyoxal (sodium bisulfite addition adduct) to afford crystalline quinoxaline trifluoroacetamide 10 (Scheme 3.8). Deprotection, salt formation, and crystallization completed the synthesis of 1 tartrate in 44% overall yield from 6 in early... 

The important advantage of a direct crystallization is that a chiral compound does not necessarily possess functional groups which are required for diastereomeric salt formation. The disadvantages include its limited applicability because less than 10% of all crystalline race-mates occur as a conglomerates, poor predictability and very sensitive dependence from the experimental conditions. Thus, as mentioned by some authors, even Louis Pasteur would not have succeeded with his very first enantioseparation had he performed the experiment with the mixed cesium-rubidium salt of tartaric acid at temperatures higher than 27 °C [4]. 

Many alkaloids may be only sparingly soluble in ether but, with the exception of pentane and hexane, their purification is more readily effected from this solvent than from any other. It is possible to prepare ether solutions of these bases of a concentration far in excess of their equilibrium value which then often yield a crystalline solid in reattaining a state of equilibrium. A supersaturated ethereal solution of these bases is readily prepared as follows The relatively dilute aqueous acid solution of the alkaloids, in a separatory funnel, is covered with a layer of ether, and a layer of water interposed between the two layers by the cautious addition of water down the side of the funnel. Aqueous ammonia is run in, in a like manner, the stopper inserted in the funnel, and the mixture shaken very vigorously. Often the more insoluble alkaloids will crystallize from the ether layer before it can be separated. In any case the wet turbid ethereal solution can be brought to brilliant clarity by treatment with charcoal. Removal of the ether leaves a residue which is now amenable to fractional crystallization from other solvents, to fractional distillation, or to salt formation. 

Colorless crystalline salt, converts to GagO on heating in air heating in vacuum at 220°C results in formation of GaN, proceeding through several stages. Crystallizes in octahedra. 

Potassium tetracyanopalladate(II) when crystallized from water forms the 3-hydrate, which is a white crystalline salt, isomorphous with the corresponding rhombic tetra-cyanoplatinate(II). The 3-hydrate is efflorescent in air it loses two molecules of water of crystallization at 100° and the thii d at 200°. When the compound is heated to moderately high temperatm-es, it decomposes with the formation of palladium, cyanogen, and potassium cyanide. The 1-hydrate is readily soluble in water and in liquid ammonia and is somewhat soluble in alcohol giving colorless solutions in each case. The addition of dilute acids to potassium tetracyanopalladate(II) precipitates pal-ladium(II) cyanide, while boiling with concentrated sulfuric acid completely decomposes the compound. 

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